Spastic paraplegia 85, autosomal recessive

Summary

Spastic paraplegia 85, autosomal recessive (MONDO:0030512) is a disease caused by RNF170 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: RNF170 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic paraplegia 85, autosomal recessive
Mondo ID	MONDO:0030512
OMIM	619686
Orphanet	631082
DOID	DOID:0112345
UMLS	C5562053
MedGen	1794263
GARD	0025586
Is cancer (heuristic)	no

Also known as: autosomal recessive spastic paraplegia type 85 · SPG85

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › complex hereditary spastic paraplegia › spastic paraplegia 85, autosomal recessive

Related subtypes (49): hereditary sensory and autonomic neuropathy with spastic paraplegia, hereditary spastic paraplegia 15, hereditary spastic paraplegia 23, spastic paraplegia-glaucoma-intellectual disability syndrome, Troyer syndrome, MASA syndrome, hereditary spastic paraplegia 11, hereditary spastic paraplegia 24, hereditary spastic paraplegia 25, hereditary spastic paraplegia 27, hereditary spastic paraplegia 26, spastic paraplegia, optic atropy, and neuropathy, hereditary spastic paraplegia 18, hereditary spastic paraplegia 32, spastic ataxia 2, hereditary spastic paraplegia 39, hereditary spastic paraplegia 45, hereditary spastic paraplegia 44, hereditary spastic paraplegia 46, hereditary spastic paraplegia 53, hereditary spastic paraplegia 49, hereditary spastic paraplegia 54, hereditary spastic paraplegia 55, hereditary spastic paraplegia 43, hereditary spastic paraplegia 57, hereditary spastic paraplegia 64, hereditary spastic paraplegia 61, hereditary spastic paraplegia 63, glutamate pyruvate transaminase 2 deficiency, hereditary spastic paraplegia 74, autosomal recessive complex spastic paraplegia type 9B, hereditary spastic paraplegia 75, spastic paraplegia-severe developmental delay-epilepsy syndrome, autosomal recessive spastic paraplegia type 76, autosomal recessive spastic paraplegia type 78, autosomal dominant complex spastic paraplegia, maternally-inherited spastic paraplegia, fatty acid hydroxylase-associated neurodegeneration, autosomal recessive spastic paraplegia type 59, autosomal recessive spastic paraplegia type 60, autosomal recessive spastic paraplegia type 66, autosomal recessive spastic paraplegia type 67, autosomal recessive spastic paraplegia type 68, autosomal recessive spastic paraplegia type 69, autosomal recessive spastic paraplegia type 70, spastic paraplegia 84, autosomal recessive, spastic paraplegia 86, autosomal recessive, kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome, autosomal recessive complex spastic paraplegia due to kennedy pathway dysfunction

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 likely pathogenic, 2 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1331699	NM_030954.4(RNF170):c.518_519del (p.Arg173fs)	RNF170	Pathogenic	no assertion criteria provided
31590	NM_030954.4(RNF170):c.595C>T (p.Arg199Cys)	RNF170	Pathogenic	criteria provided, multiple submitters, no conflicts
4082202	NM_030954.4(RNF170):c.190C>T (p.Arg64Ter)	RNF170	Pathogenic	criteria provided, single submitter
1184893	NM_030954.4(RNF170):c.396+3A>G	RNF170	Likely pathogenic	criteria provided, single submitter
1691706	NM_030954.4(RNF170):c.321T>G (p.Cys107Trp)	RNF170	Likely pathogenic	criteria provided, multiple submitters, no conflicts
638435	NM_030954.4(RNF170):c.304T>C (p.Cys102Arg)	RNF170	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930981	NM_030954.4(RNF170):c.346C>T (p.Arg116Ter)	RNF170	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1526236	NM_030954.4(RNF170):c.396G>A (p.Thr132=)	RNF170	Uncertain significance	criteria provided, single submitter
2285997	NM_001160224.2(RNF170):c.419G>A (p.Arg140His)	RNF170	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RNF170	Strong	Autosomal recessive	spastic paraplegia 85, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF170	Orphanet:631082	Autosomal recessive spastic paraplegia type 85

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF170	HGNC:25358	ENSG00000120925	Q96K19	E3 ubiquitin-protein ligase RNF170	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF170	E3 ubiquitin-protein ligase RNF170	E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF170	Transcription factor	no		Znf_RING, DUF1232, Znf_RING/FYVE/PHD

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
lateral nuclear group of thalamus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF170	281	ubiquitous	marker	lateral nuclear group of thalamus, tendon of biceps brachii, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF170	1,165

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RNF170	Q96K19	77.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of toll-like receptor 3 signaling pathway	1	4213.0×	0.002	RNF170
response to temperature stimulus	1	1532.0×	0.003	RNF170
toll-like receptor 3 signaling pathway	1	1123.5×	0.003	RNF170
adult walking behavior	1	495.6×	0.005	RNF170
response to activity	1	324.1×	0.006	RNF170
protein K48-linked ubiquitination	1	168.5×	0.009	RNF170
gene expression	1	79.9×	0.016	RNF170
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.022	RNF170
innate immune response	1	33.6×	0.030	RNF170

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RNF170	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RNF170

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF170	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.